Meldrum's acid was initially discovered in 1908 by Meldrum. However, the structure was not correctly identified for the next 40 years until it was correctly assigned by Davidson. Due to its anomalous acidity (pKa=7.3 in DMSO) Meldrum's acid has a long and rich history as an activated nucleophile and, contrary to its malonate cousin, it can be hydrolyzed easily under acidic conditions which can allow for facile elaboration not possible with malonates.
While strategies for the selective alkylation of Meldrum's acid have been well developed, such as the reductive alkylation of aldehydes, coupling and reduction of carboxylic acids, their addition to Michael acceptors, substitution of Mitsunubu reagents, and alkyl halides, addition to cationic metal allyls—the corresponding arylation is far less developed.
In contrast to alkylation of Meldrum's acid, very few methods exist for the direct alpha-arylation of Meldrum's acid. In fact, most commonly this motif is achieved via acetal or ketal formation of a malonic acid or its ketene derivative. A more direct approach would be to alpha-arylate an already existing Meldrum's acid unit. Towards this goal, Chen and Stang have shown that diaryliodonium salts can afford direct arylation of Meldrum's acid (FIG. 1A). Furthermore, Pinhey has shown that aryl-leadtriacetates undergo facile coupling with Meldrum's acid (FIG. 1B). Unfortunately, neither of these methods allows for selective monoarylation as the reaction always leads to the fully quaternerized.
Thus, what is needed are methods that allow for the selective monoarylation of Meldrum's acid that possess a tertiary center or unsymmetric quaternerized center.
Before proceeding to a description of the present invention, however, it should be noted and remembered that the description of the invention which follows, together with the accompanying drawings, should not be construed as limiting the invention to the examples (or embodiments) shown and described. This is so because those skilled in the art to which the invention pertains will be able to devise other forms of this invention within the ambit of the appended claims.